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Biomedical subjects

G M Fraser

Publications and source records attributed to G M Fraser.

At least 37 records · Page 2Linked to original sources
PubMed1997

Association between pancreatic cystadenocarcinoma, malignant liver cysts, and polycystic disease of the kidney.

Polycystic kidney disease is an autosomal dominant disease that may be associated with cystic disease of the liver. In women, the cysts may develop early and be more troublesome than in men. Cystadenocarcinoma of the pancreas is uncommon, comprising 1% of primary pancreatic malignancies. This case report is the first to describe a familial association between polycystic kidney disease and cystadenocarcinoma of the pancreas and liver in the English medical literature. A patient with autosomal dominant polycystic kidney disease (ADPKD) and multiple hepatic cysts developed cystadenocarcinoma of the pancreas with multiple malignant liver cysts. The patient's mother, sister, and niece had ADPKD, and the patient's sister also died of pancreatic cystadenocarcinoma. We believe that the development of these two disease entities in which the primary pathology is cyst formation has a genetic association.

Aged↗
PubMed1997

Negative feedback from a Proteus class II flagellum export defect to the flhDC master operon controlling cell division and flagellum assembly.

The Proteus mirabilis flagellum class I flhDC operon was isolated, and its transcript was shown to originate from a sigma70 promoter 244 bp 5' of flhD and 29 bp 3' of a putative cyclic AMP receptor protein-binding site. Expression of this regulatory master operon increased strongly as cells differentiated into elongated hyperflagellated swarm filaments, and cell populations artificially overexpressing flhDC migrated sooner and faster. A class II flhA transposon mutant was reduced in flagellum class III gene expression, as would be expected from the FlgM anti-sigma28 accumulation demonstrated in Salmonella typhimurium, but was unexpectedly also reduced in cell elongation. Here, we show that levels of flhDC transcript were ca. 10-fold lower in this flagellum export mutant, indicating that in cells defective in flagellum assembly, there is additional negative feedback via flhDC. In support of this view, artificial overexpression of flhDC in the flhA mutant restored elongation but not class III flagellum gene transcription.

Amino Acid Sequence↗
PubMed1997

Transient hepatocellular injury during attacks of cholinergic urticaria.

Cholinergic urticaria presents as wheals and erythroderma that develop in response to a variety of factors which stimulate muscarinic receptors, including exercise, heat, cold, sweat and emotional stress. We describe a 25-year-old man with ulcerative colitis who developed cholinergic urticaria diagnosed by a metacholine test. He had had seven previous attacks over 8 years, and the finding of elevated liver enzymes required admission to four different hospitals. The clinical picture was identical: urticaria, hepatosplenomegaly, lymphadenopathy and elevation of liver enzymes. The causative agent was never identified and recovery was complete, with or without antibiotic therapy. To the best of our knowledge, this is the first description of liver involvement in cholinergic urticaria noted in the English-language medical literature.

Adult↗
PubMed1997

Gastrin levels in colorectal cancer.

Our objective was to determine whether colorectal cancer tissue synthesizes and secretes biologically active gastrins resulting in a rise of gastrin levels in patients with adenocarcinoma of the colon. Blood samples for gastrin determination were taken from the artery feeding, and from the vein draining colon tumors, from a vein draining an uninvolved colon segment and from a peripheral vein. Tissue gastrin levels were measured in tumor tissues and normal mucosa taken by colonoscopic biopsy from colon cancer patients and healthy controls. The setting was a university hospital research laboratory. We had seventeen patients with colorectal cancer and 23 controls. No significant difference was found in peripheral venous blood gastrin levels between the cancer and the control groups. Serum gastrin concentration was not significantly different in the arterial blood which supplied the tumor area, the venous blood draining the tumor, the "uninvolved" mucosa or the control normal epithelium. Cancer tissue gastrin levels were lower than those measured in biopsies of uninvolved mucosa from cancer patients and normal controls. The present results show no rise of gastrin blood levels in patients with colon cancer, nor any evidence of gastrin-increased synthesis by the tumors.

Adenocarcinoma↗
PubMed1996

Long-term immunosuppression without corticosteroids after orthotopic liver transplantation: a positive therapeutic aim.

Long-term treatment with corticosteroids after orthotopic liver transplantation (OLT) may cause adverse effects, particularly hypertension, diabetes, and bone disease. The results of steroid withdrawal from long-term immunosuppression in 114 patients after OLT was reviewed. Initial treatment was with corticosteroids, azathioprine, and cyclosporine A in 76.3% and with antithymocyte globulin in 17.5%. Corticosteroids were stopped in 96 patients (84.2%) during mean follow-up of 6.7 +/- 3.9 months, and acute rejection subsequently developed in 8. By comparison 7 of 18 patients, in whom corticosteroids were continued, developed acute rejection. Six of these had received blood group (ABO)-compatible nonidentical grafts. Rates for retransplantation in the steroid withdrawal and nonwithdrawal groups were 4.2% and 22.2%, respectively, and mortality in the two groups was 14.6% and 44.4%, respectively. Azathioprine was not given or withdrawn in 28 patients in the group from which corticosteroids were also withdrawn, with no adverse effect. Diabetes mellitus improved following corticosteroid withdrawal, but there was no improvement in hypertension. We conclude that corticosteroids can be safely withdrawn in the majority of patients after OLT.

Adrenal Cortex Hormones↗
PubMed1996

Histochemical characterization of mucosal mucin in serial biopsies along the human colon.

To establish patterns of mucin staining in the colon, a differential staining method was developed separating acid mucins into sialomucins and sulfomucins, and their distribution was studied along the colon of 9 normal subjects, 6 patients with ulcerative colitis in remission and 9 with colon cancer. Serial mucosal biopsies from the cecum to the rectum, were taken at colonoscopy and stained with aldehyde-fuchsin and alcian blue. The mean score of staining intensity in normals for sialomucins was higher than for sulfomucins, 1.85 +/- 0.05 versus 0.60 +/- 0.08 (p < 0.05). A significantly lower staining score for sulfomucins was found in the descending colon and in the cecum when compared with the rectum. Ninety-seven percent of the slides were positive for sialomucins, but only 50% for sulfomucins (p < 0.05). The mean (+/- SE) staining intensity for sialomucins in the ulcerative colitis and cancer group was 1.60 +/- 0.08 and 1.60 +/- 0.05 (p = 0.002 and p < 0.05 when compared with the controls, respectively). A difference in the percentage of biopsies positive for sulfomucins, in controls and proctosigmoiditis groups, was also observed: 50.0 and 33.3%, respectively (p = 0.013). No significant change was demonstrated in the mean sulfomucin staining score comparing normal and colon cancer patients. Our results may be used as a baseline for further research on mucin staining patterns in colorectal inflammatory and neoplastic diseases.

Biopsy↗
PubMed1996

Diabetes mellitus is associated with chronic hepatitis C but not chronic hepatitis B infection.

Glucose intolerance is associated with chronic liver disease, particularly cirrhosis, and overt diabetes mellitus is two to four times more common than in the general population. Little attention has been paid to the relationship between the cause of cirrhosis and the development of glucose intolerance or whether cirrhosis is a prerequisite. We found glucose intolerance to be particularly common in patients with chronic hepatitis C, and in this retrospective study we attempt to confirm this possible association. To investigate this question we reviewed the files of 128 patients with chronic hepatitis C and 40 with chronic hepatitis B and active liver disease. Demographic, laboratory, imaging and pathology data were abstracted. The mean fasting blood glucose (+/-SD) in the hepatitis C and B groups was 160 +/- 83 and 103 +/- 18 mg/dl (P < 0.0001) with 2.5% and 39.1% respectively being overtly diabetic (P < 0.00001). However, the mean age of the hepatitis C group was much higher (45.6 +/- 12.5 vs. 60.1 +/- 12.3 years, P < 0.00001). The prevalence of diabetes was much higher among the hepatitis C patients than in the general population. Cirrhosis was not more frequent in biopsies from hepatitis C diabetic patients compared with non-diabetic or hepatitis B patients. Multivariate analysis showed that type of hepatitis and age were significant and independent predictors for developing diabetes. We conclude that there appears to be an association between diabetes mellitus and chronic hepatitis C that is not present in patients with chronic hepatitis B.

Adult↗
PubMed1996

Screening for colonic neoplastic lesions using flexible sigmoidoscopy in employees of a nuclear research center and members of collective settlements.

It has been shown that screening of average risk individuals reduces the incidence of colorectal cancer. The most effective method for screening has yet to be determined in terms of cost-effectiveness, but approximately two-thirds of colorectal neoplastic lesions are within the reach of the flexible sigmoidoscope. It has been estimated that a single such examination at the end of the sixth decade may reduce the colorectal cancer incidence by 60%. As part of a screening program for colon cancer, short colonoscopy was performed on 399 employees of a nuclear research center and 228 members of a collective settlement (kibbutz). The examinations were carried out on individuals aged > or = 40 years by two experienced endoscopists. The splenic flexure or transverse colon was reached in 95% of the procedures. Neoplastic lesions were found in 24 (6.0%) and 8 (3.5%) screenees (not significant) in the Nuclear Research Center and kibbutz populations respectively. Polyps <1 cm in diameter were significantly more common in the Nuclear Research Center population but larger polyps and cancers were not. In 47 Nuclear Research Center screenees with a family history positive in a first-degree relative, findings increased to 14.9% (P = 0.016). A family history of malignancy was found in 33.8% of kibbutz members but in only 11.8% of Nuclear Research Center employees. There was no evidence to suggest that working at the Nuclear Research Center increased the risk of colonic neoplasms. We conclude that flexible sigmoidoscopy is a valuable screening tool, especially for individuals with a first-degree relative with cancer. The yield of neoplastic lesions in the Israeli Nuclear Research Center and kibbutz populations is similar to that of the general population in the western world. Compliance rates are high in well-defined populations.

Adult↗
PubMed1995

Six patients whose perianal and ileocolic Crohn's disease improved in the Dead Sea environment.

Hyperbaric oxygen has been used in the management of perianal Crohn's disease on the assumption that tissue oxygenation is impaired. The Dead Sea region of Israel is the lowest point on earth (402 m below sea level), and therefore the oxygen pressure is increased. We hypothesized that this elevation in oxygen pressure over an extended time might be as effective as shorter periods of high-pressure oxygen in a hyperbaric chamber. So we investigated whether the Dead Sea environment might affect the activity and perianal complications of Crohn's disease. Six patients with Crohn's disease unresponsive to medical treatment spent periods of 1-3 weeks at the Dead Sea. Four patients had discharging perianal fistulas. All were given advice concerning diet, physical activity, and immersion in the Dead Sea. The Clamp-Softley modification of the Harvey-Bradshaw Crohn's disease activity index was used to assess disease activity initially and at weekly intervals during treatment. Drug therapy was tailored to patient symptoms. Mean disease activity index before treatment was 9.0 +/- 1.4 (mean +/- SEM) and after a week at the Dead Sea 3.5 +/- 1.4 (p = 0.006). After 2 weeks the index decreased to 2.0 +/- 0.4 (p = 0.037) in four patients. In one patient, complete healing of perianal fistulae occurred after 2 weeks, and in two others there was striking improvement. Two patients with active Crohn's disease and on high-dose corticosteroids were able to stop all medication during their stay. Decrease in activity index occurred rapidly, whereas the improvement in perianal disease was more gradual. The Dead Sea environment was highly effective in managing patients with severe Crohn's disease, including perianal complications in this small, uncontrolled series.

Adult↗
PubMed1995

Is there a need for diagnostic upper gastrointestinal endoscopy before cholecystectomy?

Cholecystectomy is recommended for symptomatic gallstone disease, however atypical abdominal symptoms may be incorrectly attributed to gallstones found by chance at ultrasound. High rates of post-cholecystectomy symptoms confirm that surgery is often performed inappropriately in patients whose complaints do not derive from the biliary tract. We therefore performed esophagogastroduodenoscopy (EGD) in 56 symptomatic patients with gallstones to determine if there was an alternative explanation for patient symptoms. A surgeon then assessed the patient in the light of these findings and decided whether to operate. Of 41 patients who were questioned 12.4 +/- 7.3 months after entry, 1 of 22 patients who underwent surgery, and 5 of 19 patients treated conservatively, were symptomatic (P < 0.05). In the surgical group, one of seven patients with an endoscopic finding remained symptomatic, and in the nonsurgical group one of nine patients remained symptomatic (NS). However, in patients without endoscopic findings, none of the 15 surgical patients but 4 of 10 nonsurgical patients (40.0%) remained symptomatic (P < 0.01). We conclude that patients with gallstone disease and negative EGD who undergo cholecystectomy are less likely to remain symptomatic than those treated conservatively. Thus, endoscopy of the upper gastrointestinal tract in patients with gallstones may provide important information for the surgeon, prior to the making of therapeutic decisions.

Adolescent↗
PubMed1994

Adenocarcinoma in the rectal segment in familial polyposis coli is not prevented by sulindac therapy.

Sulindac, a nonsteroidal anti-inflammatory drug, causes regression of polyps in familial polyposis coli and may prevent new lesions. However, it is not clear whether the effect of sulindac in preventing polyps also applies to carcinoma. This case report describes a patient with familial polyposis coli who developed a carcinoma in a rectal segment after subtotal colectomy and ileorectal anastomosis. She had been treated with 450 mg sulindac daily for 28 months and was free of polyps during the latter 12 months of this period. However, despite intensive endoscopic follow-up, she developed an adenocarcinoma of the rectum. This finding may have important implications for our understanding of the development of colon cancer in familial polyposis coli and the use of sulindac to prevent it. Development of de novo carcinoma in microadenomatous tissue of the rectal mucosa, which bypasses the polyp-cancer sequence, must be considered as a possibility in these patients.

Adenocarcinoma↗
PubMed1994

Increasing serum creatinine and age reduce the response to hepatitis B vaccine in renal failure patients.

The relationship between diminished response to hepatitis B vaccine in renal failure patients and serum creatinine level, age and other factors is unknown. The immune response of patients with renal failure of varying severity to hepatitis B vaccine was determined in this study. Sixty-eight patients with renal failure of varying severity who were negative for hepatitis B markers received four doses of hepatitis B vaccine, and anti-HBs titers were determined at 0, 1, 2, 3, 6, 8 and 12 months. Maximum anti-HBs titers were seen at 8 months. At this time 86% of patients with creatinine < or = 4 mg/dl but only 37% with creatinine > 4.0 mg/dl had a protective titer of > or = 10 mIU/ml (p < 0.002). Age was inversely related to anti-HBs titer (p = 0.045) and was independent of serum creatinine in predicting antibody response. We conclude that all patients with chronic renal failure should be immunized against hepatitis B as early as possible in the development of their disease, to ensure maximum response, and to minimize the effects of elevated serum creatinine and increasing age.

Adult↗
PubMed1994

Effect of panel composition on appropriateness ratings.

Cholecystectomy is performed frequently and for relatively few indications. An all surgical panel agreed on more indications and fewer contra-indications for cholecystectomy than a mixed specialty panel but did not approve indications for patients with higher comorbidity. In mixed panels subspecialists (gastroenterologists) were more conservative than generalists and surgeons. Similar findings have been shown for carotid endarterectomy. Comparing the results of British and Israeli panels showed variations in rating appropriateness that indicate differences in approach between countries. We conclude that the composition of panels will influence the assessment of appropriateness.

Cholecystectomy↗
PubMed1994

Epidemiology of Crohn's disease in southern Israel.

OBJECTIVES: Crohn's disease in Israel was described in the past as being of low incidence, more common in Europe-America-born Jews than other Jews, and of uncharacteristically low morbidity. However, recent experience has suggested that these premises are no longer correct. METHODS: The records of all hospital and outpatient cases of Crohn's disease in southern Israel for the period 1968-1992 were reviewed. Private family practitioners and specialists were contacted to assure complete case ascertainment. RESULTS: The prevalence rate of Crohn's disease among Jews on December 31, 1992, was 50.6/10(5) (Asia-Africa-born Jews 55.0/10(5), Europe-America-born Jews 58.7/10(5), and the rate was 8.2/10(5) among Bedouin Arabs. The annual incidence rate (1987-1992) was calculated as 4.2/10(5)/yr in Jews (Asia-Africa-born 4.6/10(5)/yr, Europe-America-born 3.9/10(5)/yr). The age of presentation declined progressively over the study period, was lower in Israel-born patients than immigrants, and was lower in ileocolonic versus other sites of disease. CONCLUSIONS: The data show that Crohn's disease has become more common in Jews in Israel, losing ethnic differences of frequency, and that it occurs at a younger age than before. In Arabs, the disease is more rare.

Crohn Disease↗
PubMed1993

Indications for cholecystectomy: the results of a consensus panel approach.

A consensus panel approach was used in Israel to develop a list of clinical indications for which there was agreement that cholecystectomy should be performed. Nine physicians from different disciplines were asked to score a list of 266 clinical indications for cholecystectomy. Each indication was scored on a scale of 1 (inappropriate, i.e. health risks exceed health benefits) to 9 (appropriate, i.e. benefits exceed risks). Each indication also included one of four comorbidity levels (none to high). Agreement and disagreement were defined and panelists met to discuss, modify and rescore the list. The composition of the panel and definitions of agreement had a considerable impact on the preparation of a list of agreed, appropriate indications for cholecystectomy. Gastroenterologists in the panel were less likely to recommend surgery than either surgeons or general internists both before and after the panel discussion. Following the discussion the level of agreement (defined as after discarding the highest and lowest score all of the remaining seven panelists were in a 3-point range) increased from 39% to 46% (p < 0.08) and disagreement decreased from 27% to 18% (p < 0.01). Fifty-nine of the 266 indications were considered appropriate with agreement.

Attitude of Health Personnel↗
PubMed1993

The agreed indications and contra-indications for cholecystectomy.

Indications as to which patients should undergo cholecystectomy remain, at least in part, a matter of controversy. In 1987, a panel of nine Israeli physicians from different specialties established a list of indications for the performance of cholecystectomy based on the literature available at the time. The panel agreed that cholecystectomy was appropriate for 59 indications and that it was inappropriate for 58. The major indications for surgery were biliary colic and acute cholecystitis. Patients who were asymptomatic or had vague symptoms were not recommended to undergo surgery unless they had stones in the common bile duct and were less than 71 years of age. Patients with pancreatitis were recommended for surgery if they had stones in the common bile duct and did not have a history of alcohol abuse. Performing a cholecystectomy at the same time as abdominal surgery was being performed for other reasons was indicated only if the patient was symptomatic from his gall-stones.

Acute Disease↗
PubMed1993

Validation of a centrally maintained computerized hospital database: comparison with operating room logbooks.

Substantial interest exists in variations in the use of surgical procedures by specific populations. Studies of this issue are often based on routinely collected data that are maintained in central computer systems. In this study a method is presented for examining the validity of such a database, which is maintained by Kupat Holim, in terms of sensitivity and positive predictive value by comparing its data to data from other information sources, such as operating room log books and in-patient medical records. The validation process was performed in Israel for three surgical procedures: cholecystectomy and prostatectomy each in four hospitals and hysterectomy in two hospitals. The sensitivity of the computerized database ranged from 90% to 98% and the positive predictive value from 96% to 99%. We conclude that the centrally maintained computerized database is a reliable source of information, however, when extremely accurate information is needed the use of complementary sources of information, e.g., operating room logbooks, is recommended.

Cholecystectomy↗